The long-term goal of this research is to characterize specific behavioral abnormalities in depression, their relationship to clinical, physiological, and biochemical variables, and their response to pharmacological intervention, with a view toward clarifying mechanisms and improving the treatment of depressive states. Our current interests center upon the operation of central reinforcement systems, information processing, particularly in memory, and autonomic function in states of depression and during recovery. In crossectional studies, carefully diagnosed samples of primary depressives (outpatient and inpatient, endogenous and non-endogeneous) will be compared with matched normal controls prior to treatment employing a variety of measures: clinical, subjective, behavioral and autonomic. Behavioral measures will include procedures designed specifically to measure responsiveness to reinforcement and aspects of short-term memory function. In longitudinal studies, primary depressives will be compared with themselves before and after treatment, using the measures listed above. Relationships between changes on different measures will be examined. Responses in different subgroups of depressives will be compared. The effects of standard antidepressants on the same measures will be evaluated by comparing primary depressives with themselves alternating periods of treatment with active drug and placebo. Relationships between changes on different measures will be examined, and responses in different subgroups of depressives will be compared. These studies may offer new theoretical insights into the relationship between clinical and biochemical events in depression, from the viewpoints of behavioral analysis, cognitive function and autonomic function. New methods of classifying depressives may emerge, with differential indications for treatment. Some mechanism of action of antidepressants may be suggested, as well as new procedures for evaluating antidepressants in humans and animals.